The longterm goal of the proposed research is to elucidate the mechanisms of action of opioids and antagonists at the cellular level using electrophysiological and neuropharmacological techniques. The specific aims for this project period derive from pilot studies demonstrating that naloxone increases monosynaptic and polysynaptic reflexes in naive acute spinal cats. The mechanism responsible for naloxone's facilitation of reflexes will be investigated using intracellular recording in motor neurons, excitability testing of primary afferents, and recording of spinal reflexes on ventral roots. Both reflex and single unit experiments will also be performed using other narcotic antagonists including naltrexone, nalbuphine, and oxilorphan. The effects of morphine and dextrorphan will also be studied. The interaction of morphine and naloxone will be investigate to evaluate the possibility that spinal reflexes provide an experimental model of acute dependence of morphine. The effects of chronic administration of naloxone and naltrexone on spinal reflexes and on the sensitivity of the reflexes to narcotic agonists and antagonists will be determined. The investigation of effects of naloxone is important because naloxone is often considered to be a pure narcotic antagonists with no actions of its own . It is for this reason that a long acting formulation seems especially attractive for therapeutic use. The present studies also have significant implications in experimental studies in which narcotic antagonists are used to precipitate abstinence as a measure of the degree of dependence of morphine. They may also contribute significantly to our understanding of the function of possible endogenous compounds with morphine like actions. BIBLIOGRAPHIC REFERENCE: Goldfarb, J. and Hu, J.W. Enhancement of Reflexes by Naloxone in spinal cats. Neuropharmacol., 15:785-792, 1976.